The present invention relates to a method and device for combining the sampling and analyzing of interstitial fluid or whole blood samples which is suitable for hospital bedside and home use.
The management of many medical conditions requires the measurement and monitoring of a variety of analytes in bodily fluid. Historically, the measurement of analytes in blood has required an invasive technique, such as a venipuncture or finger puncture, to obtain blood for sampling purposes. An example of an analyte which is routinely tested by obtaining a blood sample through an invasive technique is glucose. In order to control their condition, diabetics must monitor their glucose levels on a regular basis. Invasive techniques used to obtain a blood sample for analysis have the disadvantage of being painful, which can reduce patient compliance in regular monitoring. Repeated testing, e.g., on a fingertip, can result in scar tissue build-up which makes obtaining a sample in that region more difficult. Moreover, invasive sampling procedures pose a risk of infection or disease transmission.
An alternative is to sample interstitial fluid rather than whole blood. Interstitial fluid is the fluid that fills the space between the connective tissue and cells of the dermal layer of the skin. An application where interstitial fluid has been shown to be an appropriate sampling substitute for plasma or whole blood is in the measurement of glucose concentration (J. Lab. Clin. Med. 1997, 130, 436-41).
In the patents U.S. Pat. Nos. 5,879,367, 5,879,310, 5,820,570 and 5,582,184 are disclosed methods of sampling using a fine needle in conjunction with a device to limit the penetration depth to obtain small volumes of interstitial fluid for the purpose of glucose monitoring. However, there is no method disclosed for analyzing the drawn samples that is suitable for home use or hospital bedside use.
It is desirable to be able to measure the concentration of analytes in humans or other animals without having to draw a blood sample by conventional methods. It is further desirable to be able to do so with an inexpensive disposable device that is simple enough for home or hospital bedside use.
The invention provides a suitable alternative to conventional sampling devices and methods that is less invasive than traditional whole blood sampling techniques and that requires a considerably smaller sample volume than is required in the conventional venipuncture or finger puncture sampling methods. Because of the smaller sample volume required, a smaller wound is necessary to obtain the sample. In the conventional finger stick method, a drop of blood is formed on the tip of a finger, then the sensor sample entrance is wetted with the drop. Because the sample comes into contact with the skin surface, contamination of the sample by material on the skin surface is possible. The devices and methods disclosed herein do not require forming a blood drop on the surface of the skin, and therefore have less risk of sample contamination.
In one embodiment of the present invention, a fluid sampling device is provided which includes a body, the body including a dermal layer penetration probe having a penetrating end and a communicating end, and an analysis chamber having a proximal and distal end, the analysis chamber having a volume, wherein the penetration probe is in fluid communication with the analysis chamber such that fluid can flow from the penetration probe toward the analysis chamber. The analysis chamber can have at least one flexible wall which can be compressed to reduce the volume of the analysis chamber. The penetration probe can include, for example, a needle, a lancet, a tube, a channel, or a solid protrusion and can be constructed of a material such as carbon fiber, boron fiber, plastic, metal, glass, ceramic, a composite material, mixtures thereof, and combinations thereof. The penetration probe can include two sheets of material in substantial registration, having a protrusion on each sheet, wherein the sheets are spaced apart such that liquid can be drawn between the sheets by capillary action. The two sheets of material can extend into the device so as to form a pre-chamber. The penetration probe can be positioned within a recess in the proximal end of the device, and the recess can be configured to substantially align with a shape of a selected dermal surface.
In a further embodiment, the device can further include a pre-chamber having a volume and a first and second end, wherein the pre-chamber is interposed between the penetration probe and the analysis chamber such that the first end of the pre-chamber is adjacent the communicating end of the penetration probe and the second end of the pre-chamber is adjacent the proximal end of the analysis chamber. The volume of the pre-chamber can be greater than or equal to the volume of the analysis chamber. The pre-chamber can have at least one flexible wall that can be compressed to reduce the volume of the pre-chamber. The pre-chamber can also include a valve at the first end capable of substantially sealing the pre-chamber from the penetration probe.
In another embodiment, the device further includes a compressible bladder in communication with the analysis chamber, the compressible bladder being capable of applying a positive or a negative pressure to the analysis chamber.
In yet another embodiment, the pre-chamber and the analysis chamber can be capable of exerting different capillary forces. The capillary force exerted by the analysis chamber can be greater than the capillary force exerted by the pre-chamber. The differential capillary force can be derived, at least in part, from a difference between the pre-chamber height and the analysis chamber height. In this embodiment, the interior surface of the pre-chamber can include at least first and second pre-chamber walls spaced apart at a first distance to define a pre-chamber height, and the interior surface of the analysis chamber can include at least first and second analysis chamber walls spaced apart at a second distance to define an analysis chamber height, wherein the height of the analysis chamber is less than the height of the pre-chamber.
In yet another further embodiment, at least one of the chambers can include a substance capable of enhancing or diminishing the capillary force exerted by the chamber. The substance can include, for example, a polymer, a resin, a powder, a mesh, a fibrous material, a crystalline material, or a porous material. Suitable substances include polyethylene glycol, polyvinylpyrrolidone, a surfactant, a hydrophilic block copolymer, and polyvinylacetate. In a further embodiment, the device further includes a releasable actuator capable of supplying a force sufficient to cause the penetration probe to penetrate a dermal layer. The actuator can be external to or integral with the body, and upon release propels the body toward the dermal layer.
In a further embodiment, the analysis chamber can include an electrochemical cell including a working electrode and a counter/reference electrode and an interface for communication with a meter, wherein the interface communicates a voltage or a current.
In yet another embodiment of the present invention, a method for determining a presence or an absence of an analyte in a fluid sample is provided including the steps of providing a fluid sampling device as described above; penetrating a dermal layer with the penetration probe; substantially filling the analysis chamber with a fluid sample by allowing the sample to flow from the penetration probe toward the analysis chamber; and detecting a presence or an absence of the analyte within the analysis chamber. The sample can include, for example, interstitial fluid and whole blood. A qualitative or quantitative measurement of a characteristic of the sample can be obtained in the detecting step. The characteristic of the sample can include, for example, a reaction product of the analyte, such as a color indicator, an electric current, an electric potential, an acid, a base, a reduced species, a precipitate, and a gas. The analyte can include, for example, an ion such as potassium, an element, a sugar, an alcohol such as ethanol, a hormone, a protein, an enzyme, a cofactor, a nucleic acid sequence, a lipid, a pharmaceutical, and a drug. Cholesterol and lactate are examples of substances that can be analyzed.
In a further embodiment, the flow of sample toward the analysis chamber can be driven by a driving force, e.g., capillary force or a pressure differential. Where the analysis chamber has a flexible wall, the wall can be compressed to reduce the volume of the analysis chamber prior to penetrating the dermal, then the compression released to form a partial vacuum in the analysis chamber. Where the fluid sampling device further includes a compressible bladder, the bladder can be compressed to reduce its volume, then after penetration of the dermal layer the compression can be released to form a partial vacuum in the compressible bladder and analysis chamber. dr
FIG. 1 shows a top view (not to scale) of one embodiment of a sampling device illustrating an arrangement of the penetration probe, pre-chamber, and analysis chamber.
FIG. 2 shows a cross section (not to scale) along the line A-Axe2x80x2 of FIG. 1.
FIG. 3 shows a top view (not to scale) of one embodiment of a sampling device illustrating an arrangement of the penetration probe, pre-chamber, and analysis chamber wherein the proximal edge of the device forms a recess.
FIG. 4 shows a top view (not to scale) of one embodiment of a sampling device illustrating an arrangement of the penetration probe, pre-chamber, and analysis chamber.
FIG. 5 shows a cross section (not to scale) along the line B-Bxe2x80x2 of FIG. 4.
FIGS. 6a and 6b (not to scale) depict an embodiment of the invention wherein the device is loaded in a releasable actuator to facilitate penetration of a dermal layer by the penetration probe. FIG. 6a depicts the device loaded in the actuator, wherein the actuator is in the cocked position, ready to be triggered. FIG. 6b depicts the device and actuator after triggering.